Heterodimeric osteogenic factor

Abstract

The present invention provides osteogenically active protein preparations comprising a heterodimer of P3 OF 31-34 subunit B and P3 OF 31-34 subunit D, which subunits are linked with at least one disulfide bond and methods for their preparation. The invention further provides cell lines transformed with nucleotide sequences encoding P3 OF 31-34 subunit B and P3 OF 31-34 subunit D and vectors comprising those sequences in operative association with an expression control sequence.

What is claimed is: 
     
       1. An osteogenic protein preparation comprising a heterodimer of a first polypeptide subunit and a second polypeptide subunit the preparation produced according to the method of culturing in a suitable culture medium a cell line transformed with a first and a second nucleotide sequence, said first nucleotide sequence being selected from the group consisting of: the nucleotide sequence as shown in SEQ ID NO: 3; and   a nucleotide sequence which encodes the same sequence of amino acids as encoded by the nucleotide sequence shown in SEQ ID NO: 3; and said second nucleotide sequence being selected from the group consisting of:   the nucleotide sequence as shown in SEQ ID NO: 1; and   a nucleotide sequence which encodes the same sequence of amino acids as encoded by the nucleotide sequence shown in SEQ ID NO: 1; to produce said heterodimer, and isolating said preparation from the culture medium.   
     
     
       2. A pharmaceutical composition consisting of an osteogenic protein preparation according to claim 1. 
     
     
       3. A method for inducing bone formation in a mammal comprising administering to said mammal an effective amount of the osteogenic preparation of claim 1. 
     
     
       4. The method of claim 3 wherein said osteogenic preparation is admixed with a physiologically acceptable matrix material, carrier or diluent. 
     
     
       5. A composition for implantation into a mammal consisting of the osteogenic preparation of claim 1 admixed with a physiologically acceptable matrix material, carrier or diluent. 
     
     
       6. The composition according to claim 5 wherein said physiologically acceptable matrix material is selected from the group consisting of tricalcium phosphate, hydroxyapatite, collagen, plaster of paris, thermoplastic resins, polylactic acid, polyglycolic acid and polycaprolactic acid.